Agricultural livestock operations require reliable, accurate systems for detecting pregnancy in order to optimize offspring crop percent and heavy weaning weights. Cows and sheep producing offspring every 12 months and calving or ewing early in the season give the best performance. To boost the efficiency of breeding operations, it is necessary to identify non-pregnant animals.
Identification of livestock that are not pregnant as early as possible following insemination or exposure to males is key in managing reproductive cycles, because it allows producers to make decisions early regarding rebreeding strategies. In an effort to make a profit, livestock producers must strive for a high pregnancy rate, calf crop and heavy weaning weights.
Pregnancy detection procedures for livestock animals should be inexpensive, sensitive and highly accurate. One way to determine pregnancy status is to observe signs of estrus (heat) after insemination. While this approach is effective, it is expensive, labor intensive, very time consuming, and not very accurate. Other methods of pregnancy detection include detection by rectal palpation, which is more accurate that checking estrus, but also is labor intensive and not feasible early during pregnancy. The current gold standard for determining pregnancy in cattle is through rectal ultrasound on day 32 of pregnancy. Similarly, the optimum time for detecting pregnancy in sheep using transabdominal B-mode ultrasonography ranges from 25 to 110 days of gestation, optimally from 45 to 90 days of gestation.
Maternal recognition of pregnancy in ruminants requires elongation of the conceptus coinciding with production of interferon-tau (IFNT). The ovine conceptus secretes IFNT from Days 10 to 21-25 with greatest release occurring on Days 14 to 16 of pregnancy, although the precise pattern of secretion of IFNT and activation of interferon-stimulated genes (ISGs) has not been fully described. IFNT is a major product of ovine and bovine conceptuses before attachment that functions to prevent the return to estrous cycles. IFNT acts in a paracrine manner to silence up-regulation of (estradiol receptor) ESR1 and oxytocin receptor (OXTR) in the endometrial luminal epithelium and superficial glandular epithelium, thereby preventing the release of prostaglandin F2α (PGF). In addition, IFNT has recently been reported to function through endocrine action in the ovine corpus luteum (CL).
IFNT binds type 1 receptors (IFNR1 and IFNR2) and activates the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. The JAK/STAT pathway includes downstream mediators such as the signal transducer and activator of transcription (STAT)s (1 and 2), interferon regulatory factor (IRFs) and IFN-stimulated genes (ISGs). A hypothesized mechanism of how IFNT mediates maternal recognition of pregnancy is through the increased expression of several ISGs in the uterus, such as ISG15, Interferon-induced with helicase C domain 1 (IFIH1), and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58). Additionally, pregnancy induces expression of ISGs in several ovine extra uterine tissues, such as the corpus luteum (CL). ISG15, first termed ubiquitin cross-reactive protein because of its cross-reactivity with antibody against ubiquitin increases in mouse and human endometrium in response to pregnancy. ISG15 is induced by type I IFN and becomes conjugated to intracellular proteins in a mechanism parallel, but different to that described for ubiquitin.
The Inventors have previously demonstrated that sheep have increased antiviral activity in uterine vein serum (UVS) during early pregnancy. Antiviral activity is blocked in Day 15 UVS of pregnancy when preadsorbed with anti-interferon-tau (IFNT) antibodies.